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1.
Polymers (Basel) ; 16(13)2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-39000616

RESUMO

Low-density green polyethylene (LDGPE) composites reinforced with 5 wt% of bamboo fiber and 3 wt% of a compatibilizing agent (polyethylene grafted with maleic anhydride and tannin) were processed through extrusion and injection molding. Bamboo fiber, Bambusa Vulgaris, was characterized using Fourier-transform infrared spectroscopy (FTIR). The molded specimens were analyzed for their thermal, mechanical, and morphological properties. The estimated concentration was chosen to provide the best mechanical strength to the material studied. FTIR analysis of the fibers revealed the presence of groups characteristic of bamboo fiber and tannin. Differential scanning calorimetry revealed that both compatibilizing agents increased the matrix's degree of crystallinity. However, scanning electron microscopy (SEM) showed that, despite the presence of compatibilizing agents, there was no significant improvement in adhesion between the bamboo fibers and LDGPE.

2.
Polymers (Basel) ; 16(13)2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-39000643

RESUMO

Natural fiber reinforcements have the potential to enhance mechanical properties, thereby improving performance and durability in various applications. In this study, we comprehensively evaluated the impact of environmental degradation over 120 days on reprocessed polypropylene (PP) reinforced with corn husk fiber (CHF) composites. The manufactured systems underwent rigorous analysis using various techniques, including Fourier transform infrared spectroscopy, thermogravimetric analysis, optical microscopy, scanning electron microscopy, and tensile testing. These analyses revealed that climatic conditions significantly influenced (p < 0.05) the mechanical properties of all systems. Photodegradation led to surface morphological changes and chemical structures. Regardless, adding CHF filler proved a key factor, as it allowed for less susceptibility to environmental degradation than the reprocessed matrix. These findings, therefore, provide robust evidence supporting the feasibility of using CHF composites for manufacturing agricultural containers.

3.
Artigo em Inglês | MEDLINE | ID: mdl-38950840

RESUMO

Growing evidence supports dopamine's role in aversive states, yet systematic reviews focusing on dopamine receptors in defensive behaviors are lacking. This study presents a systematic review of the literature examining the influence of drugs acting on dopamine D2-like receptors on unconditioned and conditioned fear in rodents. The review reveals a predominant use of adult male rats in the studies, with limited inclusion of female rodents. Commonly employed tests include the elevated plus maze and auditory-cued fear conditioning. The findings indicate that systemic administration of D2-like drugs has a notable impact on both innate and learned aversive states. Generally, antagonists tend to increase unconditioned fear, while agonists decrease it. Moreover, both agonists and antagonists typically reduce conditioned fear. These effects are attributed to the involvement of distinct neural circuits in these states. The observed increase in unconditioned fear induced by D2-like antagonists aligns with dopamine's role in suppressing midbrain-mediated responses. Conversely, the reduction in conditioned fear is likely a result of blocking dopamine activity in the mesolimbic pathway. The study highlights the need for future research to delve into sex differences, explore alternative testing paradigms, and identify specific neural substrates. Such investigations have the potential to advance our understanding of the neurobiology of aversive states and enhance the therapeutic application of dopaminergic agents.

4.
Curr Microbiol ; 81(6): 144, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38630311

RESUMO

A group of Gram-negative plant-associated diazotrophic bacteria belonging to the genus Nitrospirillum was investigated, including both previously characterized and newly isolated strains from diverse regions and biomes, predominantly in Brazil. Phylogenetic analysis of 16S rRNA and recA genes revealed the formation of a distinct clade consisting of thirteen strains, separate from the formally recognized species N. amazonense (the closest species) and N. iridis. Comprehensive taxonomic analyses using the whole genomes of four strains (BR 11140T = AM 18T = Y-2T = DSM 2788T = ATCC 35120T, BR 11142T = AM 14T = Y-1T = DSM 2787T = ATCC 35119T, BR 11145 = CBAmC, and BR 12005) supported the division of these strains into two species: N. amazonense (BR 11142 T and BR 12005) and a newly proposed species (BR 11140 T and BR 11145), distinct from N. iridis. The phylogenomic analysis further confirmed the presence of the new Nitrospirillum species. Additionally, MALDI-TOF MS analysis of whole-cell mass spectra provided further evidence for the differentiation of the proposed Nitrospirillum species, separate from N. amazonense. Analysis of chemotaxonomy markers (i.e., genes involved in fatty acid synthesis, metabolism and elongation, phospholipid synthesis, and quinone synthesis) revealed that the new species highlights high similarity and evolutionary convergence with other Nitrospirillum species. This new species exhibited nitrogen fixation ability in vitro, it has similar NifHDK protein phylogeny position with the closest species, lacked denitrification capability, but possessed the nosZ gene, enabling N2O reduction, distinguishing it from the closest species. Despite being isolated from diverse geographic regions, soil types, and ecological niches, no significant phenotypic or physiological differences were observed between the proposed new species and N. amazonense. Based on these findings, a new species, Nitrospirillum viridazoti sp. nov., was classified, with the strain BR 11140T (DSM 2788T, ATCC 35120T) designated as the type strain.


Assuntos
Nitrogênio , Poaceae , Filogenia , RNA Ribossômico 16S/genética , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
5.
Gen Dent ; 72(3): 56-60, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38640007

RESUMO

Squamous cell carcinoma (SCC) is the type of cancer that most frequently affects the oral cavity, mainly in men older than 50 years of age. Treatment for oral SCC often involves surgical excision of the affected margins, resulting in mutilation that affects the patient's quality of life. The objective of this case report is to describe the prosthetic treatment of a 56-year-old man who underwent total glossectomy, resulting in speech and swallowing difficulties. The proposed treatment was a tongue prosthesis retained by orthodontic clasps on the mandibular first molars. After maxillary and mandibular complete-arch impressions were performed and casts were prepared for prosthetic planning, an acrylic resin plate and 3 tongue prototypes were fabricated. Esthetic and functional tests were carried out, and 2 tongue models (1 for speech and 1 for eating) were selected for acrylization, finishing, and polishing. After placement of the prostheses, the patient was referred for follow-up with a speech therapist to improve his adaptation with the prostheses. The patient was satisfied with the prostheses and able to perform the functions of chewing, swallowing, and speech production, which helped in his social reintegration and improved his quality of life.


Assuntos
Implantes Dentários , Neoplasias Bucais , Neoplasias da Língua , Masculino , Humanos , Pessoa de Meia-Idade , Glossectomia/métodos , Qualidade de Vida , Língua/cirurgia , Língua/patologia , Neoplasias da Língua/cirurgia , Neoplasias da Língua/patologia
6.
Food Sci Biotechnol ; 33(7): 1651-1659, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38623422

RESUMO

Mead is a fermented alcoholic beverage produced by yeast action on a diluted solution of honey. In this study, for the first time, sensory acceptance, purchase intention and color parameters of potentially probiotic mead with Saccharomyces boulardii were evaluated. The mead with S. boulardii presented yeast counts higher than 106 CFU/mL, being considered potentially probiotic, and tended to be yellow in color. About 160 tasters participated in the sensory evaluation, and 69.38% knew mead, but only 35.62% had tried the beverage. In terms of acceptance, the mead were within the acceptable range (above 5), and F2 (with initial soluble solids of 30° Brix and S. boulardii concentration of 0.030 g/L) was the most accepted, with an overall average of 7.63 ± 1.42 on the nine-point hedonic scale. In addition, F2 presented the highest purchase intention. In conclusion, the mead showed a tendency towards the color yellow and good sensory acceptance.

7.
Clin Sci (Lond) ; 138(4): 137-151, 2024 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-38299431

RESUMO

Hypercholesterolemia in pregnancy is a physiological process required for normal fetal development. In contrast, excessive pregnancy-specific hypercholesterolemia increases the risk of complications, such as preeclampsia. However, the underlying mechanisms are unclear. Toll-like receptor 4 (TLR4) is a membrane receptor modulated by high cholesterol levels, leading to endothelial dysfunction; but whether excessive hypercholesterolemia in pregnancy activates TLR4 is not known. We hypothesized that a high cholesterol diet (HCD) during pregnancy increases TLR4 activity in uterine arteries, leading to uterine artery dysfunction. Sprague Dawley rats were fed a control diet (n=12) or HCD (n=12) during pregnancy (gestational day 6-20). Vascular function was assessed in main uterine arteries using wire myography (vasodilation to methacholine and vasoconstriction to phenylephrine; with and without inhibitors for mechanistic pathways) and pressure myography (biomechanical properties). Exposure to a HCD during pregnancy increased maternal blood pressure, induced proteinuria, and reduced the fetal-to-placental weight ratio for both sexes. Excessive hypercholesterolemia in pregnancy also impaired vasodilation to methacholine in uterine arteries, whereby at higher doses, methacholine caused vasoconstriction instead of vasodilation in only the HCD group, which was prevented by inhibition of TLR4 or prostaglandin H synthase 1. Endothelial nitric oxide synthase expression and nitric oxide levels were reduced in HCD compared with control dams. Vasoconstriction to phenylephrine and biomechanical properties were similar between groups. In summary, excessive hypercholesterolemia in pregnancy impairs uterine artery function, with TLR4 activation as a key mechanism. Thus, TLR4 may be a target for therapy development to prevent adverse perinatal outcomes in complicated pregnancies.


Assuntos
Hipercolesterolemia , Hiperlipidemias , Animais , Feminino , Masculino , Gravidez , Ratos , Hipercolesterolemia/metabolismo , Hiperlipidemias/metabolismo , Cloreto de Metacolina/metabolismo , Fenilefrina/farmacologia , Fenilefrina/metabolismo , Placenta , Ratos Sprague-Dawley , Receptor 4 Toll-Like/metabolismo , Artéria Uterina/metabolismo , Vasodilatação/fisiologia
8.
Cardiovasc Res ; 120(4): 360-371, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38193548

RESUMO

AIMS: Heart failure with preserved ejection fraction (HFpEF) is a prevalent disease worldwide. While it is well established that alterations of cardiac energy metabolism contribute to cardiovascular pathology, the precise source of fuel used by the heart in HFpEF remains unclear. The objective of this study was to define the energy metabolic profile of the heart in HFpEF. METHODS AND RESULTS: Eight-week-old C57BL/6 male mice were subjected to a '2-Hit' HFpEF protocol [60% high-fat diet (HFD) + 0.5 g/L of Nω-nitro-L-arginine methyl ester]. Echocardiography and pressure-volume loop analysis were used for assessing cardiac function and cardiac haemodynamics, respectively. Isolated working hearts were perfused with radiolabelled energy substrates to directly measure rates of fatty acid oxidation, glucose oxidation, ketone oxidation, and glycolysis. HFpEF mice exhibited increased body weight, glucose intolerance, elevated blood pressure, diastolic dysfunction, and cardiac hypertrophy. In HFpEF hearts, insulin stimulation of glucose oxidation was significantly suppressed. This was paralleled by an increase in fatty acid oxidation rates, while cardiac ketone oxidation and glycolysis rates were comparable with healthy control hearts. The balance between glucose and fatty acid oxidation contributing to overall adenosine triphosphate (ATP) production was disrupted, where HFpEF hearts were more reliant on fatty acid as the major source of fuel for ATP production, compensating for the decrease of ATP originating from glucose oxidation. Additionally, phosphorylated pyruvate dehydrogenase levels decreased in both HFpEF mice and human patient's heart samples. CONCLUSION: In HFpEF, fatty acid oxidation dominates as the major source of cardiac ATP production at the expense of insulin-stimulated glucose oxidation.


Assuntos
Insuficiência Cardíaca , Masculino , Humanos , Animais , Camundongos , Trifosfato de Adenosina/metabolismo , Miocárdio/metabolismo , Volume Sistólico , Camundongos Endogâmicos C57BL , Ácidos Graxos/metabolismo , Glucose/metabolismo , Insulina/metabolismo , Cetonas
9.
Trop Anim Health Prod ; 56(2): 54, 2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38261022

RESUMO

This study evaluated litter performance, behavioral and physiological parameters, and milk characteristics of sows submitted to different thermal environments. Fifty sows were distributed in a completely randomized design with two treatments: an evaporative cooling system (ECS) and a conventional system (CS). Sow and its litter were characterized as an experimental unit. The animals were weighed at equalization and weaning. Feed intake, milk production, and bromatological characteristics of milk were measured; the sows respiratory rate, rectal, and surface temperature were monitored. Litter uniformity was determined at equalization and weaning. Behaviors of the sows and litters were monitored for 24 h on the 7th and 15th day of lactation. Temperature and relative humidity inside the maternity was 25.00 to 28.00 °C and 26.00 to 32.55 °C and 30.00 to 70.00% and 70.00 to 88.00%, respectively, considering ECS and CS. Nutritional quality of the milk remained stable during lactation in both systems evaluated. ECS improved the average weight of the piglets, weaning weight, and daily milk production by 0.038, 0.699, and 2.31 kg/day, respectively. Sows housed in the ECS had a reduction in physiological parameters and, increase in inactive alert behavior (1.79 percentage points) and breastfeeding behavior. Piglets showed a decrease of 2.43% in the range of feedings at night and 0.15% during the day. ECS provided better comfort to the sows at the expense of the CS and, consequently, better litter performance.


Assuntos
Lactação , Clima Tropical , Animais , Feminino , Ingestão de Alimentos , Leite , Suínos , Desmame
10.
J Pharmacol Exp Ther ; 388(1): 145-155, 2024 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-37977817

RESUMO

Heart failure with preserved ejection fraction (HFpEF) is a major health problem with limited treatment options. Although optimizing cardiac energy metabolism is a potential approach to treating heart failure, it is poorly understood what alterations in cardiac energy metabolism actually occur in HFpEF. To determine this, we used mice in which HFpEF was induced using an obesity and hypertension HFpEF protocol for 10 weeks. Next, carvedilol, a third-generation ß-blocker and a biased agonist that exhibits agonist-like effects through ß arrestins by activating extracellular signal-regulated kinase, was used to decrease one of these parameters, namely hypertension. Heart function was evaluated by invasive pressure-volume loops and echocardiography as well as by ex vivo working heart perfusions. Glycolysis and oxidation rates of glucose, fatty acids, and ketones were measured in the isolated working hearts. The development of HFpEF was associated with a dramatic decrease in cardiac glucose oxidation rates, with a parallel increase in palmitate oxidation rates. Carvedilol treatment decreased the development of HFpEF but had no major effect on cardiac energy substrate metabolism. Carvedilol treatment did increase the expression of cardiac ß arrestin 2 and proteins involved in mitochondrial biogenesis. Decreasing bodyweight in obese HFpEF mice increased glucose oxidation and improved heart function. This suggests that the dramatic energy metabolic changes in HFpEF mice hearts are primarily due to the obesity component of the HFpEF model. SIGNIFICANCE STATEMENT: Metabolic inflexibility occurs in heart failure with preserved ejection fraction (HFpEF) mice hearts. Lowering blood pressure improves heart function in HFpEF mice with no major effect on energy metabolism. Between hypertension and obesity, the latter appears to have the major role in HFpEF cardiac energetic changes. Carvedilol increases mitochondrial biogenesis and overall energy expenditure in HFpEF hearts.


Assuntos
Insuficiência Cardíaca , Hipertensão , Camundongos , Animais , Volume Sistólico , Miocárdio/metabolismo , Carvedilol/farmacologia , Carvedilol/metabolismo , Metabolismo Energético , Obesidade/complicações , Obesidade/metabolismo , Hipertensão/metabolismo , Glucose/metabolismo
11.
Int J Immunogenet ; 51(1): 20-31, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37984413

RESUMO

This study investigated the impacts of CCR5 promoter region polymorphisms on the development of systemic lupus erythematosus (SLE) by comparing CCR5 genotypes and haplotypes from SLE patients with ethnically matched controls. A total of 382 SLE patients (289 European-derived and 93 African-derived) and 375 controls (243 European-derived and 132 African-derived) were genotyped for the CCR2-64I G > A (rs1799864), CCR5-59353 C > T (rs1799988), CCR5-59356 C > T (rs41469351), CCR5-59402 A > G (rs1800023) and CCR5-59653 C > T (rs1800024) polymorphisms through polymerase chain reaction-restriction fragment length polymorphism and direct sequencing. Previous data from CCR5Δ32 analysis was included in the study to infer the CCR5 haplotypes and as a possible confounding factor in the binary logistic regression. European-derived patients showed a higher frequency of CCR5 wild-type genotype (conversely, a reduced frequency of Δ32 allele) and a reduced frequency of the HHG*2 haplotype compared to controls; both factors significantly affecting disease risk [p = .003 (OR 3.5, 95%CI 1.6-7.5) and 2.0% vs. 7.2% (residual p = 2.9E - 5), respectively]. Additionally, the HHA/HHB, HHC and HHG*2 haplotype frequencies differed between African-derived patients and controls [10% vs. 20.5% (residual p = .003), 29.4% vs. 17.4% (residual p = .003) and 3.9% vs. 0.8% (residual p = .023), respectively]. Considering the clinical manifestations of the disease, the CCR5Δ32 presence was confirmed as a susceptibility factor to class IV nephritis in the African-derived group and when all patients were grouped for comparison [pcorrected  = .012 (OR 3.0; 95%CI 3.0-333.3) and pcorrected  = .0006 (OR 6.8; 95%CI 1.9-24.8), respectively]. In conclusion, this study indicates that CCR5 promoter polymorphisms are important disease modifiers in SLE. Present data reinforces the CCR5Δ32 polymorphism as a protective factor for the development of the disease in European-derived patients and as a susceptibility factor for class IV nephritis in African-derived patients. Furthermore, we also described a reduced frequency of HHA/HHB and an increased frequency of HHC and HHG*2 haplotypes in African-derived patients, which could modify the CCR5 protein expression in specific cell subsets.


Assuntos
Lúpus Eritematoso Sistêmico , Nefrite , Humanos , Predisposição Genética para Doença , Lúpus Eritematoso Sistêmico/genética , Polimorfismo Genético , Genótipo , Nefrite/genética , Receptores CCR5/genética , Regiões Promotoras Genéticas/genética , Frequência do Gene , Polimorfismo de Nucleotídeo Único
12.
Basic Res Cardiol ; 119(1): 133-150, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38148348

RESUMO

Heart failure is a prevalent disease worldwide. While it is well accepted that heart failure involves changes in myocardial energetics, what alterations that occur in fatty acid oxidation and glucose oxidation in the failing heart remains controversial. The goal of the study are to define the energy metabolic profile in heart failure induced by obesity and hypertension in aged female mice, and to attempt to lessen the severity of heart failure by stimulating myocardial glucose oxidation. 13-Month-old C57BL/6 female mice were subjected to 10 weeks of a 60% high-fat diet (HFD) with 0.5 g/L of Nω-nitro-L-arginine methyl ester (L-NAME) administered via drinking water to induce obesity and hypertension. Isolated working hearts were perfused with radiolabeled energy substrates to directly measure rates of myocardial glucose oxidation and fatty acid oxidation. Additionally, a series of mice subjected to the obesity and hypertension protocol were treated with a pyruvate dehydrogenase kinase inhibitor (PDKi) to stimulate cardiac glucose oxidation. Aged female mice subjected to the obesity and hypertension protocol had increased body weight, glucose intolerance, elevated blood pressure, cardiac hypertrophy, systolic dysfunction, and decreased survival. While fatty acid oxidation rates were not altered in the failing hearts, insulin-stimulated glucose oxidation rates were markedly impaired. PDKi treatment increased cardiac glucose oxidation in heart failure mice, which was accompanied with improved systolic function and decreased cardiac hypertrophy. The primary energy metabolic change in heart failure induced by obesity and hypertension in aged female mice is a dramatic decrease in glucose oxidation. Stimulating glucose oxidation can lessen the severity of heart failure and exert overall functional benefits.


Assuntos
Insuficiência Cardíaca , Hipertensão , Feminino , Animais , Camundongos , Glucose/metabolismo , Camundongos Endogâmicos C57BL , Insuficiência Cardíaca/metabolismo , Miocárdio/metabolismo , Oxirredução , Cardiomegalia/metabolismo , Hipertensão/complicações , Obesidade/complicações , Ácidos Graxos/metabolismo , Metabolismo Energético
13.
World Allergy Organ J ; 16(12): 100845, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38075555

RESUMO

Background: Food allergy has considerably increased in recent years and this situation has been aggravated mainly by the consumption of more processed and complex foods, since minor or potentially allergenic foods are not required to be labeled. Manihot esculenta (cassava) is a widely consumed food in South America, Africa, and Asia and can be used in the production of flour and starch, as well as several other products. This root can cause allergic reactions with symptoms ranging from mild to severe. Methods: Thus, the aim of this study was the characterization of the immunogenic cassava proteins responsible for sensitizing patients allergic to it. Using a 2D-SDS-PAGE based proteomic approach, six proteins were identified, including Fructose Bisphosphate Aldolase (FBA). Recombinant FBA was produced in Expi293 cells and evaluated by immunoblotting with the serum of 10 individual study subjects. Results: Our results showed six cassava IgE-reactive proteins. From those, recombinant fructose bisphosphate aldolase (FBA) showed a positivity of 80% among tested sera, proving to be a highly sensitizing protein. Conclusion: The recombinant FBA molecule obtained in this study can be important for in vivo diagnostic assays, by producing more accurate results, and for desensitization protocols, in which the use of the isolated molecule produces more precise results by avoiding secondary sensitization. Trial registration: All patients signed a consent form approved by the internal ethics committee CAPPesq, Comissão de Ética para Análise de Projetos de Pesquisa do HC FMUSP (CAAE: 10420619.6.0000.0068).

14.
Psychiatry Res Neuroimaging ; 336: 111733, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37913655

RESUMO

Specific brain activation patterns during fear conditioning and the recall of previously extinguished fear responses have been associated with obsessive-compulsive disorder (OCD). However, further replication studies are necessary. We measured skin-conductance response and blood oxygenation level-dependent responses in unmedicated adult patients with OCD (n = 27) and healthy participants (n = 22) submitted to a two-day fear-conditioning experiment comprising fear conditioning, extinction (day 1) and extinction recall (day 2). During conditioning, groups differed regarding the skin conductance reactivity to the aversive stimulus (shock) and regarding the activation of the right opercular cortex, insular cortex, putamen, and lingual gyrus in response to conditioned stimuli. During extinction recall, patients with OCD had higher responses to stimuli and smaller differences between responses to conditioned and neutral stimuli. For the entire sample, the higher the response delta between conditioned and neutral stimuli, the greater the dACC activation for the same contrast during early extinction recall. While activation of the dACC predicted the average difference between responses to stimuli for the entire sample, groups did not differ regarding the activation of the dACC during extinction recall. Larger unmedicated samples might be necessary to replicate the previous findings reported in patients with OCD.


Assuntos
Medo , Transtorno Obsessivo-Compulsivo , Adulto , Humanos , Medo/fisiologia , Extinção Psicológica/fisiologia , Encéfalo/diagnóstico por imagem , Rememoração Mental/fisiologia , Transtorno Obsessivo-Compulsivo/diagnóstico por imagem
15.
Future Med Chem ; 15(17): 1553-1567, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37727967

RESUMO

Aims: The development of safe and effective therapies for treating paracoccidioidomycosis using computational strategies were employed to discover anti-Paracoccidioides compounds. Materials & methods: We 1) collected, curated and integrated the largest library of compounds tested against Paracoccidioides spp.; 2) employed a similarity search to virtually screen the ChemBridge database and select nine compounds for experimental evaluation; 3) performed an experimental evaluation to determine the minimum inhibitory concentration and minimum fungicidal concentration as well as cytotoxicity; and 4) employed computational tools to identify potential targets for the most active compounds. Seven compounds presented activity against Paracoccidioides spp. Conclusion: These compounds are new hits with a predicted mechanisms of action, making them potentially attractive to develop new compounds.


Assuntos
Paracoccidioides , Paracoccidioidomicose , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Quimioinformática , Paracoccidioidomicose/tratamento farmacológico , Testes de Sensibilidade Microbiana
17.
Adv Rheumatol ; 63(1): 30, 2023 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-37415193

RESUMO

BACKGROUND: Our aim was to compare the efficacy of rituximab, tocilizumab, and abatacept in individuals with rheumatoid arthritis (RA) refractory to treatments with MTX or TNFi agents. METHODS: We searched 6 databases until January 2023 for phase 2-4 RCTs evaluating patients with RA refractory to MTX or TNFi therapy treated with rituximab, abatacept, and tocilizumab (intervention arm) compared to controls. Study data were independently assessed by two investigators. The primary outcome was considered as achieving ACR70 response. RESULTS: The meta-analysis included 19 RCTs, with 7,835 patients and a mean study duration of 1.2 years. Hazard ratios for achieving an ACR70 response at six months were not different among the bDMARDs, however, we found high heterogeneity. Three factors showing a critical imbalance among the bDMARD classes were identified: baseline HAQ score, study duration, and frequency of TNFi treatment in control arm. Multivariate meta-regression adjusted to these three factors were conducted for the relative risk (RR) for ACR70. Thus, heterogeneity was attenuated (I2 = 24%) and the explanatory power of the model increased (R2 = 85%). In this model, rituximab did not modify the chance of achieving an ACR70 response compared to abatacept (RR = 1.773, 95%CI 0.113-10.21, p = 0.765). In contrast, abatacept was associated with RR = 2.217 (95%CI 1.554-3.161, p < 0.001) for ACR70 compared to tocilizumab. CONCLUSION: We found high heterogeneity among studies comparing rituximab, abatacept, and tocilizumab. On multivariate metaregressions, if the conditions of the RCTs were similar, we estimate that abatacept could increase the chance of reaching an ACR70 response by 2.2-fold compared to tocilizumab.


Assuntos
Antirreumáticos , Artrite Reumatoide , Humanos , Abatacepte/uso terapêutico , Rituximab/uso terapêutico , Metotrexato/uso terapêutico , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Antirreumáticos/uso terapêutico , Metanálise em Rede , Artrite Reumatoide/tratamento farmacológico
18.
Arq Neuropsiquiatr ; 81(8): 756-763, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37402400

RESUMO

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a viral infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although respiratory manifestations have received greater visibility during the pandemic caused by this virus, numerous neurological complaints related to coronavirus 2 infection have been documented in several countries. These records suggest that this pathogen presents neurotropism, and it can cause different neurological conditions of varying intensity. OBJECTIVE: To investigate the ability of coronavirus 2 to invade the central nervous system (CNS) and its neurological clinical outcomes. METHODS: The present study consists in a comprehensive literature review of the records available in the PubMed, SciELO, and Google Scholar databases. The descriptors COVID-19, brain and physiopathology, associated with the Boolean operator AND, were used in the search. Regarding the inclusion and exclusion criteria, we selected the papers published since 2020 with the highest number of citations. RESULTS: We selected 41 articles, most of them in English. The main clinical manifestation associated with COVID-19 patients was headache, but cases of anosmia, hyposmia, Guillain-Barré syndrome, and encephalopathies were also described with considerable frequency. CONCLUSION: Coronavirus-2 presents neurotropism, and it can reach the CNS by hematogenous dissemination and by direct infection of the nerve endings. It causes brain injuries through several mechanisms, such as cytokine storm, microglial activation, and an increase in thrombotic factors.


ANTECEDENTES: A doença do coronavírus 2019 (coronavirus disease 2019, Covid-19, em inglês) é uma infecção viral provocada pelo coronavírus 2 da síndrome respiratória aguda grave (severe acute respiratory syndrome coronavirus 2, SARS-CoV-2, em inglês). Embora as manifestações respiratórias tenham recebido maior visibilidade ao longo da pandemia provocada por esse vírus, inúmeras queixas neurológicas relacionadas à infecção pelo coronavírus 2 foram documentadas em diversos países. Tais registros sugerem que esse patógeno apresenta neurotropismo, e é capaz de provocar quadros neurológicos diversos e de intensidade variáveis. OBJETIVO: Investigar a capacidade de invasão do sistema nervoso central (SNC) pelo coronavírus 2 e seus principais desfechos clínicos neurológicos. MéTODOS: O presente estudo consiste em uma ampla revisão de literatura a partir dos registros das bases de dados PubMed, SciELO e Google Acadêmico. Nesse contexto, os descritores COVID-19, cérebro e fisiopatologia, associados com o operador booleano AND, foram utilizados na busca. Quanto aos critérios de inclusão e exclusão, selecionou-se os trabalhos publicados a partir de 2020 com o maior número de citações. RESULTADOS: Foram selecionados 41 artigos, a maioria na língua inglesa. A principal manifestação clínica associada a pacientes acometidos pela COVID-19 foi a cefaleia, mas casos de anosmia, hiposmia, síndrome de Guillain-Barré e encefalopatias também foram descritos com frequência considerável. CONCLUSãO: O coronavírus 2 apresenta neurotropismo, e é capaz de alcançar o SNC por disseminação hematogênica e por infecção direta das terminações nervosas. Ele provoca injúria cerebral por meio de variados mecanismos, como tempestade de citocinas, ativação da micróglia e aumento dos fatores trombóticos.


Assuntos
COVID-19 , Doenças do Sistema Nervoso , Humanos , COVID-19/complicações , COVID-19/patologia , SARS-CoV-2 , Doenças do Sistema Nervoso/etiologia , Sistema Nervoso Central , Encéfalo/patologia
19.
Metabolism ; 146: 155613, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37295715

RESUMO

BACKGROUND: Eosinophils are generally related to helminth infections or allergies. Their association with metabolic alterations and adipose tissue (AT) remodeling has been demonstrated mainly in animal models of obesity. However, their physiological role in driving metabolic features has not yet been well described. Herein, we aimed to evaluate the participation of eosinophils in metabolic and adipose tissue homeostasis in mice and humans, focusing on a translational perspective. MATERIAL AND METHODS: Male BALB/c wild-type (WT) mice and GATA-1 knockout (Δdb/GATA-1-/-) mice were followed until 16-week-age in a regular diet or were fed with a high-refined-carbohydrate (HC) diet or high-fat (HF) diet for eight weeks. In subjects with obesity, clinical parameters and omental AT gene expression were evaluated. RESULTS: Eosinophils lack in mice fed a regular diet induced insulin resistance and increased adiposity. Their adipose tissue showed augmented cytokine levels, which could be attributed to increased leukocytes in the tissue, such as neutrophils and pro-inflammatory macrophages. Bone marrow transplant from WT mice to Δdb/GATA-1-/- mice showed some improvement in glucose metabolism with lower adipose tissue mass accretion. Upon an unhealthy diet challenge, Δdb/GATA-1-/- mice fed HC diet showed a mild degree of adiposity and glucose metabolic dysfunction severe in those mice fed HF diet. The expression of eosinophil markers in omental AT from humans with severe obesity was positively correlated to eosinophil cytokines and insulin sensitivity surrogate markers and negatively correlated to systemic insulin, HOMA-IR, and android fat mass. CONCLUSIONS: Eosinophils seem to have a physiological role by controlling systemic and adipose tissue metabolic homeostasis by modulating glucose metabolism, inflammation, and visceral fat expansion, even in lean mice. Indeed, eosinophils also seem to modulate glucose homeostasis in human obesity.


Assuntos
Eosinófilos , Resistência à Insulina , Masculino , Humanos , Animais , Camundongos , Lactente , Eosinófilos/metabolismo , Obesidade/genética , Obesidade/metabolismo , Tecido Adiposo/metabolismo , Citocinas/metabolismo , Resistência à Insulina/genética , Dieta Hiperlipídica , Glucose/metabolismo , Camundongos Knockout , Camundongos Endogâmicos C57BL
20.
Surg Neurol Int ; 14: 161, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37292397

RESUMO

Background: Harvey Cushing and collaborators created the first society of neurosurgeons in 1920, in the United States of America, the Society of Neurological Surgeons. In 1955, the World Federation of Neurosurgical Societies (WFNS) was created in Switzerland to improve neurosurgical care globally through the scientific cooperation of members. The performance of neurosurgical associations today is fundamental to discuss diagnostic methods and therapeutic approaches, transforming modern medicine. Although most neurosurgical associations are recognized worldwide, there are some societies that are not recognized internationally due to a lack of regulatory bodies and lack of official digital channels, among other reasons. The main objective of the article is to list the neurosurgical societies and to provide a more integrated view of the interactions between neurosurgical societies in different countries. Methods: We developed a table summarizing the countries recognized by the United Nations, the continents, capitals, name of the present societies, and social networks. We utilized "Country AND (Neurosurgery OR Neurological Surgery) AND (Society OR Association)," in English, and in the native language of the country. Our search included: PubMed, Scopus, Google, Google Scholar, and the WFNS website, without filters. Results: We found 189 neurosurgery associations, from 131 countries and territories; 77 countries did not have their own neurosurgical societies. Conclusion: There is a difference between the number of internationally recognized societies, and the number of societies found in this study. In the future, we should better organize neurosurgical societies in countries that have neurosurgical activity with those without such resources.

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